Quinolone carboxylic acids or naphthyridine carboxylic acids are used in the treatment of patients having various conditions. Most often, quinolone carboxylic acids or naphthyridine carboxylic acids are used as anti-infective agents. The term "patient" means humans and other animals.
One way to deliver quinolone carboxylic acids or naphthyridine carboxylic acids to a patient is via a parenteral route. For example, a suitable solution of or a suitable formulation containing the quinolone carboxylic acid or naphthyridine carboxylic acid compounds can be injected into muscle tissue or the blood stream.
Formulation of parenteral dosage forms of quinolone carboxylic acids or naphthyridine carboxylic acids typically starts with the corresponding bulk drug substance prepared in its free base form. Chemical synthesis of the free base form of the quinolone carboxylic acids or naphthyridine carboxylic acids often involves hydroxide ion induced neutralization of an acid salt derivative of the quinolone carboxylic acid or naphthyridine carboxylic acid.
Poor filtration rates during the processing of bulk drug substances can cause major product quality problems including increased difficulties in washing out low level impurities from the product. In addition, when slow, inefficient filtration occurs, it is often necessary to use rework procedures to assure a thorough wash of the product.
Longer filtration times or rework procedures should be avoided because they result in increased time of exposure of the product to the environment and a corresponding greater chance for biological contamination of the product. Furthermore, a slow filtration procedure will normally add additional cost to the product because additional processing time requires extra labor. Moreover, these problems are magnified upon scale-up to commercial quantities.
The present invention provides a method of making quinolone carboxylic acids or naphthyridine carboxylic acids in free base form that provides for dramatically improved filtration rates. The present invention uses trace levels of calcium (II) salts, which results in products having improved filtration rates.